How do you diagnose extramedullary hematopoiesis?

Diagnosis of Extramedullary Hematopoiesis

Extramedullary hematopoiesis (EMH) is diagnosed through a combination of clinical context (underlying hematologic disorder), characteristic imaging findings, and tissue confirmation when imaging is non-diagnostic or when malignancy cannot be excluded. 1, 2

Clinical Context and Initial Assessment

• Identify underlying hematologic conditions that predispose to EMH, including myelofibrosis, thalassemia, sickle cell disease, diffuse osseous metastatic disease replacing bone marrow, and leukemia 2, 3
• Obtain complete blood count with differential to assess for cytopenias and evaluate peripheral blood smear for dysplastic features 4
• Perform bone marrow examination (core biopsy and aspirate with immunophenotyping and cytogenetics) to document inadequate bone marrow function or ineffective erythropoiesis that drives compensatory EMH 5, 3
• Measure hemoglobin levels, as patients with EMH typically present with anemia (mean hemoglobin around 7.9 g/L in documented cases) 6

Imaging-Based Diagnosis

First-Line Imaging Approach

• Order CT or MRI as the primary imaging modality to detect and characterize EMH masses based on anatomical location 1, 2
• Recognize location-specific patterns: EMH most commonly presents in the liver, spleen, lymph nodes, and paravertebral regions (thoracic spine) 2, 3, 6

Characteristic Imaging Features by Location

Thoracic (Paravertebral) EMH:

• Look for bilateral paravertebral fat-containing masses in the lower thoracic spine, which is the most diagnostically specific presentation 2
• These masses typically do not present a diagnostic dilemma when fat is visible 2

Abdominal EMH:

• Hepatosplenomegaly is the most common manifestation but is non-specific without focal masses 2
• Focal soft-tissue masses may appear in liver, spleen, perirenal space, and peritoneum 2
• Many abdominal masses lack adipose elements, making diagnosis challenging 2

Imaging Characteristics of Established EMH:

• Older lesions demonstrate hemosiderin and fat deposition, making them easier to diagnose 1
• Newer, actively hematopoietic lesions often mimic neoplasms and lack characteristic features 1

Advanced Imaging When Diagnosis is Uncertain

• Perform 99mTc-labeled sulfur colloid scintigraphy (molecular imaging) when CT/MRI findings are equivocal, as this demonstrates active hematopoietic tissue 1
• Consider PET/CT if extramedullary disease is suspected in patients with acute myeloid leukemia or plasma cell disorders 5
• Use MRI for intraspinal EMH to evaluate for cord compression, which requires urgent treatment 3

Tissue Diagnosis

Indications for Biopsy

• Perform tissue biopsy when imaging alone is non-diagnostic and cannot confidently differentiate EMH from neoplasm (lymphoma, metastatic disease, sarcoma) 1, 2
• Biopsy is mandatory when there is no known underlying hematologic disorder and EMH presents as an isolated mass 7
• Consider biopsy for atypical locations including intraspinal canal, presacral region, nasopharynx, paranasal sinuses, and synovial joints 3, 7

Biopsy Technique and Precautions

• Plan biopsy carefully given the high propensity for hemorrhage in EMH masses 2
• Screen for coagulopathy by evaluating prothrombin time, partial thromboplastin time, and fibrinogen before any invasive procedure 5
• Ensure adequate platelet support is available before biopsy 5

Cytological Features on Fine-Needle Aspiration

• Expect a variable mixture of bone marrow elements including megakaryocytes (0-6%), myelocytes and metamyelocytes (18-33%), erythroid precursors (0-7%), polymorphs (10-36%), blasts (0-4%), eosinophils (0-7%), and lymphocytes (21-60%) 6
• Lymph nodes are the most common biopsy site (80% of cases), followed by paravertebral areas (20%) 6

Diagnostic Algorithm

Step 1: Establish clinical context with complete blood count, peripheral smear, and bone marrow examination to document underlying hematologic disorder 4, 6

Step 2: Perform CT or MRI based on suspected anatomical location 1, 2

Step 3: If imaging shows characteristic features (paravertebral fat-containing masses or masses with hemosiderin/fat deposition in a patient with known hematologic disorder), diagnosis can be made without biopsy 1, 2

Step 4: If imaging is non-diagnostic or masses lack characteristic features, obtain 99mTc sulfur colloid scintigraphy 1

Step 5: If diagnosis remains uncertain or malignancy cannot be excluded, proceed to image-guided biopsy with appropriate hemorrhage precautions 1, 2

Critical Pitfalls to Avoid

• Do not assume hepatosplenomegaly alone indicates EMH, as this is non-specific and requires additional focal masses or clinical context for diagnosis 2
• Do not biopsy without considering hemorrhage risk; ensure coagulopathy is corrected and platelet support is available 5, 2
• Do not dismiss slow-growing masses as benign without tissue diagnosis in patients without known hematologic disorders, as EMH can occur in hematologically noncompromised patients 7
• Recognize that actively hematopoietic lesions mimic neoplasms and require a high index of suspicion based on clinical background and combination of imaging findings 1

Follow-Up and Monitoring

• Monitor stable EMH masses with serial imaging to ensure stability, particularly in atypical locations 3
• Treatment is only required when symptoms are present (e.g., cord compression, obstructive symptoms), with options including blood transfusion, radiotherapy, hydroxyurea, or surgical resection 3